Hua Medicine, a leading innovative drug development company in China, has started a multicenter, multi-dose Phase 1b Trials for Diabetes. The company had previously obtained positive results from a Phase 1a trial evaluating HMS5552, a glucokinase activator (GKA) for Type 2 Diabetes, and demonstrated, even at single doses, significant effects in a variety of biochemical diabetes markers such as glucose and glucose-stimulated insulin release (GSIR).

In the Phase 1a study, groups of healthy volunteers were treated with HMS5552 in increasingly higher dose groups. In a dose-dependent manner, HMS5552 consistently increased post-meal GSIR multiple-fold above the post-meal insulin levels seen in the placebo group, with very low risk for hypoglycemia.

"Having abnormally high blood glucose levels after a meal is typical of diabetics and pre-diabetics with impaired glucose tolerance or IGT. Asian patients in particular are at even higher risk for diabetes and IGT compared to Western patients, because of both dietary and genetic factors. In particular, Chinese diabetics suffer from an earlier deterioration in beta cell function. That's why these Phase 1a results showing higher GSIR profiles were important in affirming that HMS5552 should be particularly beneficial in treating Chinese and Asian-dominant diabetics," said Yi Zhang, M.D., Director of Clinical Development at Hua Medicine.

The Phase 1a study of HMS5552 was a blinded, placebo-controlled, dose-escalation study in 60 healthy volunteers. The study was designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and MOA-validation of HMS5552. HMS5552 was evaluated in six single ascending doses ranging from 5mg, 10mg, 15mg, 25mg, 35mg and 50mg, with each dose group having 10 randomized patients (2 placebo, 8 on drug) per group. The trial demonstrated the following.

The total adverse events (AE) rate was identical vs. placebo with no relationship between AEs and incidence, types, intensity, or dose of drug. There were no severe AEs, deaths, or premature withdrawals due to AEs, and no significant laboratory, vital signs, or ECG abnormalities

Excellent linear correlation between drug dose and plasma exposure, dose-proportional AUC and Cmax across all 6 dose groups, no PK gender differences between male and female subjects, and no major metabolites were seen in plasma at the highest 50mg tested dose group

"In addition to the robust glucose and insulin responses, the substantial increase in post-meal GLP-1 levels demonstrated by HMS5552 at the higher doses was very gratifying to observe. No previous GKA in the clinic had shown significant effects on patient plasma GLP-1 levels, but our pre-clinical models suggested that HMS5552 could indeed increase GLP-1," stated CEO of Hua Medicine, Li Chen. "This effect appears to persist in our Phase 1a trials, and if confirmed in future trials would mark a significant advance in diabetes treatment, since GKA would be affecting most of the major glucose-regulation pathways in the body including insulin secretion, postprandial glucose control, hepatic glucose production, and GLP-1 modulation. We hope this multi-pathway targeting strategy will eventually lead to better, more effective therapies to control disease progression for all patients, but especially the subtype of earlier-stage diabetic patients most predominant in China and Asia."

As a follow-up to these positive Phase 1a trials, the company is now initiating a multicenter Phase 1b trial in diabetic patients that is expected to complete by 3Q-2014. The Phase 1b trial is a randomized, double-blind, placebo-controlled, multiple-ascending dose trial in 50 diabetic adult males and female patients. Daily doses will range from 25 mg to 200 mg (and up to 400 mg if needed) in the trial. In addition to evaluating HMS5552's safety, tolerability, and pharmacokinetics, the trial will evaluate the associated hormone biomarkers and pharmacodynamics of multiple oral doses of HMS5552 over a period of two weeks. These results are expected to further support HMS5552's novel mechanism of action and give guidance for trial design and optimal patient selection in future Phase 2 and Phase 3 trials.